Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification
Role of stromal and epithelial estrogen receptors in vaginal epithelial proliferation, stratification, and cornification
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DOI：
10.1210/en.139.10.4345
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发表时间：
1998-10-01
期刊：
影响因子：
4.8
通讯作者：
Cooke, PS
中科院分区：
文献类型：
--
作者：
Buckanan, DL;Kurita, T;Cooke, PS
雌二醇17-β(E-2)诱导阴道上皮细胞增殖、复层和角化。我们的目的是确定上皮和间质雌激素受体-α(ER-α)在这些E-2诱导的事件中各自的作用。从成年ERα基因敲除小鼠(Ko)和新生BALB/c小鼠(Wt)用酶法分离阴道上皮(E)和间质(S)，用来制备4种上皮、间质或两者都缺乏功能Era的组织重组体。将组织重组体移植到雌性裸鼠体内，然后摘除卵巢，并用OIL或E。对于E，处理，wt-S(wt-S+wt-E和wt-S+Ko-E)制备的移植物上皮标记指数也有类似的显著增加，这表明在wt-S+Ko-E组织重组体中，E-1刺激了上皮细胞的增殖，但缺乏上皮期。相反，在用Ko-S(Ko-S+wt-E和Ko-S+Ko-E)制备的重组体中，即使在Ko-S+wt-E移植物中检测到上皮ERα，E-2或油处理后的上皮标记指数仍保持在基线水平。在E-2处理的宿主的wt-S+wt-E移植物中，有上皮角化，而在所有其他组织重组体中，上皮没有角化。由E-2处理的宿主的wt-S+wt-E组成的移植物具有高度复层的上皮，而在E-2处理的宿主中生长的wt-S+Ko-E组织重组体的上皮厚度减少了近60%，而在所有其他组织重组体中均萎缩。此外，细胞角蛋白10是上皮分化的标志，在E-2处理的宿主中生长的wt-S+wt-E组织重组体中有较强的表达，而在所有其他组织重组体中显著减少或缺失。这些结果表明，E-2诱导的阴道上皮细胞增殖是通过间质ERα间接介导的，这与我们最近在子宫中的发现一致。相反，E-2诱导的角化和正常的上皮层化都需要上皮和间质ERα。这是已知的第一批体内上皮性ERα的功能，也是首次发现上皮对E-2的反应同时涉及间质和上皮性ERα。
Estradiol 17-beta (E-2) induces epithelial proliferation, stratification, and cornification in vaginal epithelium. Our aim was to determine the respective roles of epithelial and stromal estrogen receptor-alpha (ER alpha) in these E-2-induced events. Vaginal epithelium (E) and stroma (S) from adult ER alpha knockout (ko) and wild-type (wt) neonatal Balb/c mice were enzymatically separated and used to produce four types of tissue recombinants in which epithelium, stroma, or both lack functional ERa. Tissue recombinants were grafted into female nude mice, which were subsequently ovariectomized and treated with oil or E,. In response to E, treatment, grafts prepared with wt-S (wt-S + wt-E and wt-S + ko-E) showed similar large increases in epithelial labeling index, indicating that E, stimulated epithelial proliferation despite a lack of epithelial ERa in wt-S + ko-E tissue recombinants. Conversely, in tissue recombinants prepared with ko-S (ko-S + wt-E and ko-S + ko-E), epithelial labeling index remained at baseline levels after E-2 or oil treatment, even though epithelial ER alpha were detected in ko-S + wt-E grafts. Epithelial cornification was present in wt-S + wt-E grafts from E-2-treated hosts, whereas epithelium in all other tissue recombinants failed to cornify. Grafts composed of wt-S + wt-E from E-2-treated hosts had highly stratified epithelium, whereas epithelial thickness was reduced almost 60% in wt-S + ko-E tissue recombinants grown in E-2-treated hosts and was atrophic in all other tissue recombinants. In addition, cytokeratin 10, a marker of epithelial differentiation, was strongly expressed in wt-S + wt-E tissue recombinants grown in E-2-treated hosts but was markedly reduced or absent in all other tissue recombinants. These results indicate that E-2-induced vaginal epithelial proliferation is mediated indirectly through stromal ER alpha, consistent with our recent findings in uterus. Conversely, both epithelial and stromal ER alpha are required for E-2 induced cornification and normal epithelial stratification. These are the first known functions attributed to epithelial ER alpha in vivo and the first time any epithelial response to E-2 has been shown to involve both stromal and epithelial ER alpha.